Abstract : The aim of this research project is to define the molecular events leading to the development of PhIP-induced breast tumors and to assess if PhIP exposure at human dietary levels present a human breast cancer risk. Within the last year, we have completed pharmacokinetic studies in both male and female rats following acute oral administrations of PhIP and have determined dose-response relationships for PhIP-DNA adduct formation in the liver, colon and breast tissue. In order to identify the specific adducts formed in these tissues, we are in the process of characterizing adducts formed in vitro using the techniques of mass spectrometry and NMR. In collaboration with Miriam Poirier at NIH, we have now produced poly clonal antibodies against PhIP-DNA, which have been used in fluoro immunoassay to quantify PhIP-DNA adducts. This assay currently has a detection limit of 33 adducts/10 to the minus 9th power nucleotides using 20 micrograms DNA per analysis. Furthermore, tritium AMS methodology has now been used in conjunction with 14C AMS to conduct the first low-level double-labeling experiment utilizing 2 different compounds.